The major objective of this project is to develop new radiopharmaceuticals specific for imaging CNS dopamine receptors. In conjunction with single photon emission computed tomography (SPECT), the proposed dopamine specific agents may provide a convenient tool for measuring the dopamine receptor population. Therefore, it may improve our understanding on the progression and also on the management of this disease. Two dopamine receptor specific agents; (125I) IBZP and (125I) IBZM, specific for D-1 and D-2 dopamine receptor, respectively, have been prepared and evaluated in rats. The digital autoradiography study showed that after an iv injection in rats, these two agents localized in caudate-putamen, substantia nigra, and accumbens nucleus, areas of brain known to have high concentration of D-1 and D-2 receptors. Based on the preliminary data, we propose to synthesize the optically active isomers of IBZM and IBZP and their analogs, study the radiochemistry and kit formulation, and evaluate digital autoradiography using multiple isotopes (I-123 and I-125) with both normal and parkinsonian (MPTP treated) animal models in mice and monkeys. For two promising compounds, toxicity data will be obtained and they may be evaluated in humans by the SPECT imaging. These new dopamine receptor imaging agents may provide a convenient and non-invasive technique for evaluation of parkinsonian patients. The diagnostic information obtained with these agents may not be attainable through other diagnostic techniques.